Glucocorticoids cause cleft palate in mice. A glucocorticoid binding substance with receptor-like properties has been found in fetal tissue. We wish to determine whether this receptor is associated with glucocorticoid produced cleft palate. Three approaches will be used. 1) The relationship between mouse strain susceptibility and receptor interaction will be explored further. Glucocorticoid binding experiments with fetal cell supernatant have indicated no differences in amount of receptor between mouse strains. We propose that strain differences may be due to receptor accessibility in vivo. Pregnant mice will be injected either with unlabeled glucocorticoid or with vehicle alone. Fetal cell supernatant will be incubated with 3H-triamcinolone acetonide and bound radioactivity will be measured. The difference in radioactivity bound between control and glucocorticoid treated animals will indicate the amount of administered glucocorticoid bound. 2) Progestins, which do not cause cleft palate, compete with 3H-triamcinolone acetonide for the receptor in supernatant. Progestins will be tested as antagonists of cleft palate formation by glucocorticoids. They will also be tested for their ability to bind at the glucocorticoid site when administered in vivo as described in (1). 3) Fractionation of the 3H-triamcinolone acetonide-receptor complex on DEAE-agarose has revealed two peaks of bound radioactivity. We will test for any relationship between these peaks. We will also determine relative peak amounts: a) during the sensitive period of gestation; b) in mouse strains with differing cleft palate susceptibility; and c) in the presence of competing steroids. An understanding of the biochemical basis of cleft palate susceptibility in mice should provide a basis for better understanding human susceptibility to teratogens, and how these problems can be predicted and prevented.